Structural analysis of human specific cytolysin intermedilysin aiming application to cancer immunotherapy

Intermedilysin (ILY) is a human specific cytolysin secreted by Streptococcus intermedius. In the present study, we performed molecular modeling of ILY and cholesterol-dependent cytolysins (CDCs) (pneumolysin, PLY; listeriolysin O, LLO; streptolysin O, SLO; alveolysin, ALV; suilysin, SLY; pyolysin, PLO) to compare the membrane binding domains including the undecapeptide (11mer) region which is thought to be necessary for the cytolytic activity of CDCs.

The molecular models of cytolysins were constructed using InsightII with Homology module with X-ray data of perfringolysin O (PFO).

The ILY molecule was long and rod shaped, and comprised four domains. ILY was shown to possess stereocomplementary surfaces within the molecule and the potential to stack with 8 degrees of curvature leading to a ring cluster of 45 molecules or so in the human erythrocyte cell membranes.

From the molecular orbital calculations and isostatic potential analysis, we considered that the ILY 11mer region has different features from those of traditional CDCs, and the ILY domain 4 should be very useful to apply the human cell-specific targeting module.